Gene Sequencing May Reveal Risks for Rare Diseases

MONDAY, June 26, 2017 -- "Genome sequencing" of healthy people reveals that some are at risk for rare genetic diseases, a new study shows.

And doctors need to be sensitive when revealing that information, the researchers said.

"Sequencing healthy individuals will inevitably reveal new findings for that individual, only some of which will have actual health implications," said study lead author Dr. Jason Vassy. He's a clinician investigator at Brigham and Women's Hospital in Boston.

Vassy and his colleagues said they found "reassuring evidence" that doctors can be trained to manage their patients' sequencing results appropriately.

Moreover, "patients who receive their results are not likely to experience anxiety connected to those results," Vassy said in a hospital news release.

Whole genome sequencing entails analysis of the 3 billion pairs of letters in someone's DNA. Scientists anticipate the technology will usher in a new era of predicting and preventing disease, but how people will react to this personal information is a big question mark.

For this study, the researchers analyzed nearly 5,000 genes associated with rare genetic conditions in 50 healthy people. The investigators found that 11 of the people -- almost one-quarter -- had gene variants predicted to cause previously undiagnosed rare disease.

Two of those 11 patients had signs or symptoms of the underlying conditions. One had variants linked to an eye disease called fundus albipunctatus, which impairs night vision. The second had a variant associated with variegate porphyria, which explained the patient's mysterious rashes and sun sensitivity.

The other nine patients had no evidence of the diseases predicted by the genetic testing. For example, two patients had gene variants associated with heart rhythm abnormalities, but their hearts showed no signs of problems. It's possible, but not certain, that they could develop heart problems in the future, the study authors said.

As part of the study, the patients' primary care doctors were taught how to interpret a one-page report of their patients' genome testing results. They also had access to genetic specialists for consultation. The doctors then used their own judgment in deciding how to handle their patients' test results.

While the findings appear promising, "continued research on the outcomes of sequencing will be needed before the routine use of genome sequencing in the primary care of generally healthy adults can be medically justified," Vassy said.

Study co-author Dr. Heidi Rehm said the team was "surprised" to see how many ostensibly healthy individuals are carrying a risk variant for a rare genetic disease.

"This suggests that the potential burden of rare disease risk throughout our general population could be far higher than previously suspected," said Rehm, an associate professor of pathology at Harvard Medical School.

However, she said the likelihood that someone carrying one of these variants will eventually develop the disease is not fully known.

The study was published June 26 in the journal Annals of Internal Medicine.

More information

The U.S. National Human Genome Research Institute has more on genetic testing.